Project description:Gut microbial dysbiosis can play a causal role of in colorectal cancer. Gut microbiota chnages with age and becomes moer pro-inflammatory. We sought to determine whether microbiota from Old donors promotes more tumor formation in recipients than meterial from young donors.
Project description:Gut microbial dysbiosis can play a causal role of in colorectal cancer. Gut microbiota chnages with age and becomes moer pro-inflammatory. We sought to determine whether microbiota from Old donors promotes more tumor formation in recipients than meterial from young donors.
Project description:Colorectal cancer (CRC) is closely related to gut dysbiosis. We investigated the effects of imbalanced gut microbiota on the progression of intestinal adenoma in Apcmin/+ mice model using fecal microbiota transplantation (FMT). Administration of feces from CRC patients increased tumor proliferation and decreased apoptosis in tumor cells. Abnormal expression of genes related to Wnt-protein binding and lipid metabolic process was observed.
Project description:Gut microbiota dysbiosis characterizes systemic metabolic alteration, yet its causality is debated. To address this issue, we transplanted antibiotic-free conventional wild-type mice with either dysbiotic (“obese”) or eubiotic (“lean”) gut microbiota and fed them either a NC or a 72%HFD. We report that, on NC, obese gut microbiota transplantation reduces hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-transplanted mice. Of note, this phenotype is blunted in conventional NOD2KO mice. By contrast, lean microbiota transplantation did not affect hepatic gluconeogenesis. In addition, obese microbiota transplantation changed both gut microbiota and microbiome of recipient mice. Interestingly, hepatic gluconeogenesis, PEPCK and G6Pase activity were reduced even once mice transplanted with the obese gut microbiota were fed a 72%HFD, together with reduced fed glycaemia and adiposity compared to non-transplanted mice. Notably, changes in gut microbiota and microbiome induced by the transplantation were still detectable on 72%HFD. Finally, we report that obese gut microbiota transplantation may impact on hepatic metabolism and even prevent HFD-increased hepatic gluconeogenesis. Our findings may provide a new vision of gut microbiota dysbiosis, useful for a better understanding of the aetiology of metabolic diseases. all livers are from NC-fed mice only.
Project description:Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune receptor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators were largely intact in Aim2-deficient mice, however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with wild-type healthy mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer. We used microarrays to compare the transcriptome Aim2 deficent mice to wild type mice in colon tumor and colitis samples. Here were 12 mice in total, 3 for each genotype and tissue combination.
Project description:Gut dysbiosis is closely involved in the pathogenesis of inflammatory bowel disease (IBD). However, it remains unclear whether IBD-associated gut dysbiosis plays a primary role in disease manifestation or is merely secondary to intestinal inflammation. Here, we established a humanized gnotobiotic (hGB) mouse system to assess the functional role of gut dysbiosis associated with two types of IBD - Crohn's disease (CD) and ulcerative colitis (UC). In order to explore the functional impact of dysbiotic microbiota in IBD patients on host immune responses, we analyzed gene expression profiles in colonic mucosa of hGB mice colonized with healty (HC), CD, and UC microbiota.
Project description:Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of the gram-positive pathogenic and reduction of bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. In this study, we establish a link between the two phenomena, namely gut barrier compromise and dysregulated bile acid metabolism. We show for the first time that morphine fosters significant gut microbial dysbiosis and disrupts cholesterol/bile acid metabolism. Changes in the gut microbial composition is strongly correlated to disruption in host inflammatory homeostasis13,14 and in many diseases (e.g. cancer/HIV infection), persistent inflammation is known to aid and promote the progression of the primary morbidity. We show here that chronic morphine, gut microbial dysbiosis, disruption of cholesterol/bile acid metabolism and gut inflammation; have a linear correlation. This opens up the prospect of devising minimally invasive adjunct treatment strategies involving microbiome and bile acid modulation and thus bringing down morphine-mediated inflammation in the host.
Project description:This study aims to elucidate the impact of gut microbiota alterations on tumorigenesis and immune response in lung adenocarcinoma (LUAD). Using Gprc5a-/- mice as a model, we performed fecal microbiota transfer (FMT) from Gprc5a-/- and Gprc5a-/-; Lcn2-/- donors to investigate the role of gut microbiome changes in modulating tumor growth and the immune microenvironment. Single-cell RNA sequencing (scRNA-seq) was conducted on colonic lamina propria and subcutaneous tumor tissues. Our findings demonstrate that gut microbiota from Lcn2-deficient mice promotes systemic inflammation and immunosuppression, enhancing tumor progression. This study provides insights into the microbiome's influence on LUAD and potential therapeutic strategies targeting microbiome-related pathways.
Project description:DNA methylation profile of mouse sperm from conventionally-raised mice and gut dysbiosis experienced mice were characterized using whole-genome bisulfite sequencing. Genome-wide DNA methylation changes between control and dysbiotic male�s sperm were highly comparable, with no change in DNAme globally or at genomic features, only 21 differentially methylated regions (DMR) were identified, which did not overlap known regulatory elements. Epididymal sperm samples were harvested from 11 weeks old inbred male mice that were experiencing gut microbiota dysbiosis for 6-week (antibiotics treated, n=5), or drink sterilized water (control, n=5).